POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN PEDIATRIC LIVER-TRANSPLANTATION - INTERPLAY BETWEEN PRIMARY EPSTEIN-BARR-VIRUS INFECTION AND IMMUNOSUPPRESION

The incidence, risk factors, and outcome of post-transplant lymphoprol iferative disease (PTLD) were examined for 298 children undergoing liv er transplantation. The overall incidence of PTLD was 8.4% (25 of 298) . Intensity of immunosuppression was found to be a major risk factor f or the development of PTLD. Cyclosporine and tacrolimus when used as p rimary immunosuppression were associated with the development of PTLD in 4.3% and 6.6% of cases (P=NS). OKT3 and tacrolimus, when used as re scue therapy for steroid-resistant rejection, were associated with a c omparable increase in the risk of developing PTLD (10.9% and 11.1%, P= NS). Patients requiring both OKT3 and tacrolimus to treat refractory r ejection were at significantly increased risk for PTLD (28.1% vs. 4.3% or 6.6%, (P<0.0001). PTLD was more common in patients who received tr ansplants for Langerhans cell histiocytosis relative to other indicati ons for transplantation (66% vs. 8.4%, P=0.0005). The data also suppor t an association between primary Epstein-Barr virus (EBV) infections f ollowing transplantation and the development of PTLD. While only three patients were EBV seropositive before transplantation (14%), 19 patie nts were EBV seropositive at the time of diagnosis of PTLD (90%), conf irming a high incidence of primary EBV infections in patients with PTL D (21 patients had both pre- and posttransplant EBV serologies). In th is series, PTLD was associated with a mortality rate of 60%, and 12 of the 15 patients who died had persistent tumor at the time of death. F ive of the 13 patients rendered disease-free developed ductopenic reje ction. Of the four with severe liver dysfunction, two have undergone s uccessful retransplantation and are alive without evidence of PTLD. In conclusion, intense immunosuppression using OKT3 and tacrolimus as re scue agents was associated with a significant increase in the incidenc e of PTLD. Primary EBV infection after transplantation further accentu ated this risk. Independent of these risk factors, patients with Lange rhans cell histiocytosis were at significantly increased risk for PTLD . The identification of high-risk patients should allow the developmen t of protocols to screen patients for primary EBV infections and early indications of PTLD, as well as the institution of preemptive antivir al and antitumor therapies.